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Evaluation and management of neonatal Graves' disease

INTRODUCTION

A small percentage of mothers with hyperthyroidism caused by Graves' disease have neonates with hyperthyroidism. Although neonatal Graves' disease is self-limited, it can be severe, even life-threatening, and have deleterious effects on neural development. Maternal Graves' disease is by far the most common cause of neonatal hyperthyroidism. Depending on the balance of the maternal stimulating antibody and antithyroid drug, the fetus may be either hyperthyroid or hypothyroid. (See "Diagnosis and treatment of hyperthyroidism during pregnancy".)

INCIDENCE

Graves' hyperthyroidism occurs in approximately 0.2 percent of women, and it occurs in approximately 2 percent of infants born to these mothers [1,2]. Thus, neonatal Graves' hyperthyroidism would be expected to occur in approximately 1:25,000 neonates. Neonatal Graves' hyperthyroidism affects males and females equally.

Why only 2 percent of infants of mothers with Graves' hyperthyroidism are affected is probably related to the maternal serum concentration of thyrotropin receptor-stimulating antibodies (TSHR-SAb). The higher the maternal serum TSHR-SAb concentration during the third trimester, the greater the likelihood of neonatal Graves' hyperthyroidism. In practice, neonatal hyperthyroidism is most likely when the TSHR-SAb activity of maternal serum is above 500 percent of the values in serum of normal subjects [3,4]. This was illustrated in a study of 29 pregnant women with a history of Graves' disease that confirmed the relationship of high TSHR-SAb and neonatal thyrotoxicosis. In the 35 live births, there were six cases of neonatal Graves' disease resulting in an incidence of 17 percent, a higher rate than previously reported [5].

PATHOGENESIS

Neonatal (and fetal) Graves' hyperthyroidism results from the transplacental passage of maternal TSHR-SAb [2,6,7]. While most infants are born to women with active Graves' hyperthyroidism, the disorder can also occur in infants of women with a history of Graves' hyperthyroidism treated with thyroidectomy or radioactive iodine in the past [8]. As described above, measurement of maternal serum TSHR-SAb may be helpful in predicting whether a newborn will be affected. (See "Diagnosis and treatment of hyperthyroidism during pregnancy".)

Serial in utero ultrasonography with measurement of fetal thyroid size has also been reported to help determine which neonates are likely to manifest neonatal hyperthyroidism [9]. In a report of 20 pregnant women with Graves' disease, the fetal thyroid gland was enlarged in five pregnancies. In these five patients, the maternal antithyroid dose was decreased resulting in a reduction of the fetal thyroid gland to a normal size in three cases but in the other two cases the gland remained enlarged. These latter two infants both developed neonatal Graves' disease [9].
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